This project seeks to develop novel immunologic therapies for allergic diseases as well as the laboratory techniques required to understand their mechanism of action and rational application. We have developed the means, using both flow cytometry and real time quantitative PCR to evaluate allergen specific T cell responses with a sensitivity heretofore not possible. We have recently completed a phase II study of soluble IL-4 receptor as an anti-inflammatory/Th2 tolerogenic therapy for asthma and are in the process of analyzing the results. We have developed an in vitro model to examine the induction of allergen specific tolerance using costimulatory blockers such as CTLA-4 Ig and anti-B7. This model allows the pre-clinical evaluation of potential strategies for the therapeutic induction of immunological tolerance to allergens. We have applied a similar approach to mouse vaccine models to understand how DNA vaccines generate specific immune responses. We have shown that the long lasting immune response to DNA vaccines is due to persistent IL-12 induced by immunostimulatory sequences in the DNA. Additionally, we have identified a novel role for CD8 cells in providing IFN-gamma mediated "help" to Th1 cells in the context of DNA vaccination.